Abstract
Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in the L-tryptophan-kynurenine pathway, which converts an essential amino acid, L-tryptophan, to N-formylkynurenine. It has been speculated that IFN-gamma is a dominant IDO inducer in vivo. The present study used IFN-gamma or TNF-alpha gene-disrupted mice and IFN-gamma antibody-treated mice to demonstrate that lipopolysaccharide (LPS)-induced systemic IDO is largely dependent on TNF-alpha rather than IFN-gamma. IFN-gamma-independent IDO induction was also demonstrated in vitro with LPS-stimulated monocytic THP-1 cells. These findings clearly indicate that there is an IFN-gamma-independent mechanism of IDO induction in addition to the IFN-gamma-dependent mechanism.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies / pharmacology
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Cytokines / antagonists & inhibitors
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Cytokines / physiology
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Enzyme Induction / drug effects
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Gene Deletion
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Humans
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / genetics
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Interferon-gamma / physiology*
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Lipopolysaccharides / pharmacology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Tryptophan Oxygenase / genetics
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Tryptophan Oxygenase / metabolism*
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / physiology
Substances
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Antibodies
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Cytokines
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Lipopolysaccharides
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Interferon-gamma
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Tryptophan Oxygenase